In the present study, we found that ZNF687 could directly target and activate BMI1, NANOG and OCT4 in HCC cells, whereas individually silencing BMI1, NANOG or OCT4 potently reduced tumorsphere formation and the SP+ subpopulation in ZNF687-overexpressing HCC cells. This evidence concerns the gene POU5F1 and hepatocellular carcinoma.